tbuckley/cabot-search huggingface dataset:
Pevonedistat plus belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome: A phase I multicenter study.
Authors: Keri Renee Maher, Danielle Schafer, Dale Schaar, Roy Sabo, Dipankar Bandyopadhyay, Steven Grant
Journal: Journal of Clinical Oncology (2023)

e19015 Background: Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy, with particularly dismal prognosis in the relapsed or refractory (R/R) setting, with a median overall survival of approximately 6 months. There has been increasing interest in novel therapeutic approaches to intelligently harness cellular pathways to improve outcomes in this difficult to treat population. Pevonedistat, a first-in-class NEDD8 inhibitor, and Belinostat a HDAC inhibitor work synergistically in AML cells and human xenograft AML models supporting the clinical rationale for this Phase I study. Methods: A Phase I dose-escalation study with a 3+3 design was performed to assess safety and tolerability of pevonedistat plus belinostat. Beliniostat (D1-5) and Pevonedistat(D1,3,5) were administered in a 21 day cycle until disease progression or unacceptable toxicity. Primary endpoint was identification of MTD/RP2D, secondary endpoints included toxicity, efficacy, pharmacokinetic interactions, and pharmacodynamic studies. Results: 18 patients (67% female; median age 67.5 (41-74)), 16 of whom had AML, were treated at 5 dose levels (belinostat 800-1000mg/m2, pevonedistat 20-50mg/m2), no dose limiting toxicities were noted. Average number of prior lines of therapy was 3. Most Grade 3 or 4 toxicities were hematologic (Table). Maximum number of cycles reached was 8. Best response was stable disease in four patients, and CR in one patient. The remainder had progressive disease or were not evaluable. Most common reason for discontinuation was disease progression (67%), 11% treatment ended per protocol criteria, 6% pursued alternative therapy, 6% due to side effects. The patient achieving CR was a 54 year old female with BRAF and TET2 mutation, primarily refractory to 7+3 and also unresponsive to second line azacitidine and venetoclax. After CR, she received an allogeneic stem cell transplant and remains in remission with 2 years of follow up. Conclusions: The combination of pevonedistat plus belinostat is safe in adult R/R AML with a manageable, primarily hematologic profile, and modest but notable activity in this heavily treated population. This regimen may be effective as a bridge to transplant in some patients. MTD was not reached in this study. Clinical trial information: NCT03772925 . [Table: see text]
Impact of economic inequality on Kaposi sarcoma of the lung: A retrospective cohort.
Authors: Nehemias Guevara, Garry Francis-Morel, Esmirna Perez, Jean Gabriel Bustamante Alvarez
Journal: Journal of Clinical Oncology (2023)

e18920 Background: Kaposi Sarcoma of the lung is a rare entity; it is unclear if a below-average household income has an impact on outcomes. Methods: This is a retrospective cohort study of patients with Kaposi Sarcoma of the lung that were admitted to acute care from 2016 to 2020. Data is derived from the National Inpatient Sample (NIS). We compared outcomes in 2 cohorts: those with household income &lt; $50,000 versus those with &gt; $50,000. The primary endpoint was differences in all-cause in-patient mortality. Secondary endpoints included differences in length of stay (LoS) and admission cost. Results: A total of 460 patients met inclusion criteria; 40% had income &lt; $50K, and 60% &gt; $50K (p &lt; 0.001). There was a trend to male predominance (100% of &lt; $50K, 95% &gt; $50K; p 0.147) with a mean age of 39 (35 for &lt; 50K, 41 for &gt; 50K; p 0.015). Black patients were the most afflicted group (46%; 71% of &lt; $50K, 29% &gt; $50K; p &lt; 0.001), followed by White patients (33%, 20% of &lt; $50K, 43% of &gt; $50K; p &lt; 0.001). Additionally, patients with household income &lt; $50K (40%; p &lt; 0.001) and hospitals located in the South (43%, 48% of &lt; $50K, 40% of &gt; %50K; p &lt; 0.001) and West (32%, 11% of &lt; $50K, 46% of &gt; 50K; p &lt; 0.001) represented the largest group. Majority of patients were under Medicaid insurance coverage, however there was no relationship between Medicaid coverage and mortality (p = 0.709, CI 0.16-3.42). There was no difference in distribution based on primary payer, hospital bed size, hospital teaching status, and hospital ownership (p &gt; 0.05). No differences in mortality were noted among groups (p 0.845). No differences in LoS were seen (p 0.560), but younger patients were more likely to have shorter LoS (p 0.033). Ultimately, no differences in hospitalization costs were noted (p 0.426). Furthermore, from the 460 patients with Kaposi lung sarcoma, 5 were post-transplant patients, and 130 were patients with HIV; in this sub-group of analysis, were no differences between ages. The mean age in patients with lung transplants was 39.5, and the HIV group was 40 years. The black population was the most affected, with an income below $50 000. Conclusions: Income did not impact mortality in patients admitted for Kaposi sarcoma of the lung. Black patients and patients with income &lt; $50,000 represented the largest group. Nevertheless, more research is needed for better stratification and to elucidate many factors that play a role in the mortality of patients with Kaposi sarcoma of the lung.
Associations of loneliness and mortality risk among cancer survivors in the United States.
Authors: Jingxuan Zhao, Jennifer B. Reese, Xuesong Han, Robin Yabroff
Journal: Journal of Clinical Oncology (2023)

6531 Background: Loneliness (i.e., the subjective feeling of being isolated from others), has been linked to multiple adverse health outcomes, including chronic conditions such as heart disease, mental health disorders, and higher risk for early mortality. However, associations between loneliness and worse health outcomes have not been thoroughly examined in cancer survivors. This study examined associations between loneliness and mortality risk among cancer survivors in the U.S. Methods: Cancer survivors were identified from the 2008-2018 Health and Retirement Study, a nationally representative longitudinal survey conducted biannually among individuals aged ≥50 years, with follow-up was through December 31, 2020. Loneliness was measured at every 4 years using an abbreviated 11-item version of the UCLA Loneliness Scale Version 3. Example items include feelings of lacking companionship and isolation from others. Items were summed to create total loneliness scores, which were categorized into four levels: 11-12 (low/no loneliness), 13-15 (mild loneliness), 16-19 (moderate loneliness), and 20-33 (high loneliness). Time-varying Cox proportional hazard models were used to examine the association of loneliness and mortality risk among cancer survivors, while accounting for measurements at multiple time points. Sex, marital status, educational attainment, number of health conditions other than cancer, and year since cancer diagnosis were included in multivariable models. Results: Among 5808 person-years, there were 724 deaths during the study period. Compared to the low/no loneliness group, survivors reporting greater loneliness had higher hazard ratios (HR), indicating higher mortality risks; the highest HR observed was among the high loneliness group (HR:1.90, 95%CI:1.58-2.29), following a dose-response association (Table). HRs were attenuated after adjusting for sociodemographic characteristics, but findings were largely unchanged, and HRs remained highest for the high loneliness group (HR:1.71, 95%CI:1.39-2.12). Conclusions: Any elevated loneliness was associated with higher mortality risks among cancer survivors. Programs to screen for loneliness among cancer survivors and to provide social support to those in need are warranted. [Table: see text]
Cost effectiveness of a personalized approach for lung cancer screening with LDCT based on the use of blood-based biomarker test.
Authors: Ehsan Irajizad, Johannes Fahrmann, Jody Vykoukal, Kim-Anh Do, Jennifer Dennison, Edwin J. Ostrin, Samir M Hanash
Journal: Journal of Clinical Oncology (2023)

e18927 Background: We previously reported that a circulating panel of protein biomarkers together with a risk model based on subject characteristics improves lung cancer risk assessment for lung cancer screening compared to current screening eligibility criteria (JCO 2022 PMID 34995129). The goal of this study is to assess cost-effectiveness of a personalized approach to lung cancer screening with LDCT. Methods: We conducted retrospective analyses using data from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and protein biomarker data measured on prospectively collected pre-clinical sera from the PLCO biorepository. For determination of cost-effectiveness of using the biomarker test for risk based referral for LDCT, we assumed screening of 27.0 million US ever smokers. The reference scenario assumed eligibility using the risk-based smoking approach with no cost. We predicted that the proportion of upcoming lung cancer cases categorized as screening eligible will increase as a result of biomarker-informed eligibility. We used direct NLST costs using 2009 Medicare prices for screening (per person screened), workup (per positive screen), and treatment (per lung cancer case) and evaluated the effectiveness at different biomarker costs. We used life year gained for cases and non-cases, with and without screening. Results: With 80.4% sensitivity at 66.9% specificity; performance of our previously established lung panel, assuming a willingness-to-pay threshold of $70 000 per life-year gained, the biomarker test for referral to screening is cost-effective up to 300$. At a willingness-to-pay threshold of $100,000 per life-year, the biomarker test is cost-effective up to $500. Conclusions: A cost effective blood-based biomarker test has been developed for referral for lung cancer screening with LDCT.
SHR-1701 in combination with platinum-based chemotherapy and BP102 (a bevacizumab biosimilar) for persistent, recurrent, or metastatic cervical cancer: Data from a phase 1b/3 study.
Authors: Jihong Liu, Yun Zhou, Yili Wang, Jing Wang, ShanBing Wang, Jin Li, Xiaohong Wang, DaPeng Li, Li Wang, Fan Liang, Xianfeng Zhou, Linna Wang
Journal: Journal of Clinical Oncology (2023)

5529 Background: Platinum-based chemotherapy (chemo) ± bevacizumab is the standard first-line therapy for cervical cancer, regardless of PD-L1 expression. SHR-1701 is a novel bifunctional fusion protein targeting PD-L1 and TGF-βRII, and shows promising efficacy and controllable safety in pretreated patients (pts) with cervical cancer. This ongoing phase 1b/3 study aims to assess the addition of SHR-1701 to standard first-line therapy. Methods: In the phase 1b part, eligible pts had persistent, recurrent, or metastatic squamous-cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix not previously treated with systemic chemo for recurrence or metastasis and not amenable to curative treatment. Prior chemo-radiotherapy was permitted for recurrence, if mono-chemo was used as sensitizer. Pts were given SHR-1701 (30 mg/kg), paclitaxel (175 mg/m 2 ), cisplatin (50 mg/m 2 ) / carboplatin (AUC 5), and BP102 (15 mg/kg) every 3 weeks. The primary endpoints were safety and ORR. Results: From Feb 26 to Aug 12, 2022, 31 pts were enrolled. Median age was 55 years (range, 27-71). 24 (77.4%) had squamous-cell carcinoma, and 7 (22.6%) had adenocarcinoma. 20 (64.5%) had metastatic disease, 7 (22.6%) had recurrent cervical cancer, and 4 (12.9%) had persistent cervical cancer. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 25 (80.6%) pts, with the most common being decreased neutrophil count (n=16, 51.6%), decreased white blood cell count (n=12, 38.7%), and anemia (n=8, 25.8%). TRAEs led to discontinuation of any study agent in 8 (25.8%) pts; of note, only 2 (6.5%) pts discontinued SHR-1701 due to TRAEs (grade 3 infusion reaction and grade 3 immune-mediated rash). No treatment-related deaths occurred. Efficacy outcomes are summarized in Table. ORR was 77.4%, with 4 CRs and 20 PRs; responses were ongoing in all 24 responders. DCR was 93.5%. Shrinkage in target lesions was observed in 30 (96.8%) pts. PFS rate at 6 months reached 93.5%. Conclusions: SHR-1701 plus platinum-based doublet chemo and BP102 provided a manageable safety profile and potent antitumor activity in pts with persistent, recurrent, or metastatic cervical cancer, supporting the subsequent randomized, double-blind, placebo-controlled phase 3 part. Clinical trial information: NCT05179239 . [Table: see text]
Cost-utility analyses of later-line treatments for metastatic colorectal cancer (mCRC) by network meta-analysis (NMA) approach: Conventional constant hazard ratio vs novel survival curves methodologies.
Authors: Mavis Obeng-Kusi, Brian L Erstad, Denise Roe, Ivo Abraham
Journal: Journal of Clinical Oncology (2023)

e18928 Background: Cost-utility analyses of later-line treatments for metastatic colorectal cancer (mCRC) differ based on network meta-analysis (NMA) approach: conventional constant hazard ratio vs novel survival curves methodologies. Methods: We conducted a CUA estimating the incremental cost utility ratio (ICUR) over a 5-year time horizon from the US payer perspective. The 3-state partitioned survival models included efficacy inputs from a novel one-step multivariate NMA of progression-free and overall survival curves and from a conventional constant hazard ratio NMA. Utilities, as well as drug acquisition, administration, adverse event, monitoring and end of life costs were sourced from literature. We compared results and examined statistical factors in either approach that may explain the observed results. Results: The multivariate NMA produced lower estimates of survival benefits over placebo compared to the NMA based on constant hazard ratios, at the same incremental costs (Table). This reduction in incremental benefits led to higher estimates of cost-effectiveness and cost-utility when using the multivariate NMA. Probabilistic sensitivity analyses showed greater uncertainty in the model based on the constant hazard NMA. Conclusions: The multivariate NMA produced lower estimates of survival benefits over placebo compared to the NMA based on constant hazard ratios, at the same incremental costs (Table). This reduction in incremental benefits led to higher estimates of cost-effectiveness and cost-utility when using the multivariate NMA. Probabilistic sensitivity analyses showed greater uncertainty in the model based on the constant hazard NMA. [Table: see text]
Oncologists’ receipt of pharmaceutical industry payments and use of non-recommended and low-value cancer care services.
Authors: Aaron Philip Mitchell, Stacie B Dusetzina, Akriti Mishra Meza, Niti U. Trivedi, Peter Brian Bach, Aaron N Winn
Journal: Journal of Clinical Oncology (2023)

6639 Background: Personal payments from the pharmaceutical industry to US physicians are common and influence physician practice. Prior studies have found that industry payments sway physicians’ selection among effective, medically appropriate treatments. However, whether industry payments may be associated with non-recommended and low-value care has not been assessed. The objective of this study was to estimate the association between oncologists’ receipt of industry payments and use of non-recommended and/or low-value (NR/LV) interventions. Methods: Population-based cohort study using fee-for-service Medicare claims and Open Payments records of industry payments. We identified four NR/LV cancer interventions: 1) denosumab for castrate-sensitive prostate cancer; 2) GCSF for patients at low risk for neutropenic fever; 3) nab-paclitaxel instead of paclitaxel for breast and lung cancer 4) branded drug instead of a generic or biosimilar. Study sample: Medicare beneficiaries with an incident cancer diagnosis (identified by new occurrence of a cancer diagnosis code in proximity to claims for cancer treatment) from 2014-2019. We applied additional requirements as appropriate to identify four sub-cohorts, corresponding to patients at risk for each of the NR/LV treatments, and identified the treating oncologist using claims. The primary exposure was receipt, by a patient’s oncologist, of any industry payments for the corresponding NR/LV treatment of interest, within 365 days before the patient’s index cancer date. The primary outcome was receipt of the corresponding NR/LV treatment. We fit general linear models controlling for patient characteristics and calendar year. To assess robustness, we also accounted for physician-level fixed effects in separate models. Results: Cohort sizes were: denosumab N = 9,799; GCSF N = 271,485; nab-paclitaxel N = 86,394; branded drug N = 13,386. Controlling for patient characteristics and calendar year, industry payment was associated with an increase in the absolute prevalence of denosumab (+17.5% [95%CI:15.3 to 19.7%]), GCSF (+5.8% [95%CI:5.4 to 6.1%]), and nab-paclitaxel (+7.6% [95%CI:7.1 to 8.1%]) use, but lower branded drug use (-4.6 [95%CI:-5.8 to -3.3]). In physician-level fixed effects models, industry payment was associated with increased denosumab (+7.4% [95%CI:2.5 to 12.2%]) and nab-paclitaxel (+1.7% [95%CI:0.9 to 2.5%]) use, but not with GCSF (+0.4% [95%CI:-0.3 to 1.1%]) or branded drugs (+1.2% [95%CI:-5.8 to 8.3%]). Conclusions: Recent receipt of industry payments by physicians was associated with increased use of several forms of NR/LV cancer treatment. These findings raise quality-of-care concerns regarding physician-industry financial relationships. Additional work is needed to further explore the causal relationship between payments and non-recommended treatments, and between payments and patient outcomes.
Demographic factors associated with time to treatment initiation in hepatocellular carcinoma.
Authors: Joseph Bettag, Michael Seraphin, Weston Kroes, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2023)

e18546 Background: Hepatocellular carcinoma (HCC) accounts for 75% of all liver cancer diagnosis in the United States, with incidence rising in recent years. One aspect of treatment is time to treatment initiation (TTI). TTI is associated with better outcomes and lower patient anxiety. We hypothesize that demographic factors play a role in how fast a patient with HCC receives treatment. Methods: This study looked at 112,615 patients diagnosed with HCC from 2004-2019 in the National Cancer Database (NCDB). Demographic factors analyzed were biological sex, race, age, cancer stage, year of diagnosis, insurance status, household income, Charleson-Deyo score, and type of facility for treatment. Histology was determined using ICD-O-3 coding. Cross tabulation analysis was performed using ANOVA. Results: Patients with delayed TTI were more often male, black, stage III, 61-70 years old, on government insurance, diagnosed between 2016-2019, made less than $40,227, and treated at integrated cancer network programs. Patients with no insurance received a TTI 4 days faster than government insurance (p &lt; .001). Patients with lower incomes also experienced greater than 2-day delays in TTI (p &lt; .001) compared to higher incomes. Treatment at an integrated cancer network was associated with a 3-day delay compared to treatment at a community cancer center (p &lt; .001). Males began treatment a half day after female patients (p &lt; .017). Conclusions: Discrepancies exist in TTI for HCC patients, most notably for insurance status, race, year of diagnosis, income, and facility type. This data can be used when determining which patients may experience delays in TTI due to demographic factors.
Role of <i>BRCA1</i> promotor methylation (<i>BRCA1</i><sup>meth</sup>) in homologous recombination deficiency (HRD) in high-grade epithelial ovarian cancer.
Authors: Alain G Zeimet, Simon Schnaiter, Daniel Uwe Reimer, Katharina Wimmer, Esther Schamschula, Katharina Leitner, Katharina Steger, Christian Marth, Heidi Fiegl
Journal: Journal of Clinical Oncology (2023)

e17592 Background: In TCGA data BRCA1 meth was found to be inferior to BRCAmut regarding prognosis in high-grade ovarian cancer. This was explained by a probably lower sensitivity to platinum-based chemotherapy. Methods: In 151 high-grade epithelial ovarian cancers (HGOC) tested for BRCA status, BRCA DNA methylation was determined using MethyLight PCR. Additionally, genome-wide loss of heterozygosity (LOH) and Aneuploidy Normalized Telemetric imbalance (ANTI) by means of SNP-Array analysis (GSA-24 v 3.0/Ilumina) as surrogates for “genomic scaring” in BRCA-independent HRD. For both parameters a “clinical-threshold” was calculated on the basis of platinum-response determined at the first recurrence according to the platinum-free interval. Both variables were integrated in a common HRD-Score with a cut-off value of ≥ 10.3 for HRD positivity. Results: In the present cohort PFS of BRCA1 meth HGOC (n = 15; 10%) was not revealed to be inferior to BRCAmut HGOC. Worst PFS was observed in the subgroup of BRCAwt-unmethylated HGOC (p = 0.013) as compared to HGOC with genetic and epigenetic BRCA alterations. In line, neither LOH nor ANTI and consecutively also HRD-Score did prove to be statistically different in BRCAmut - and BRCA1meth-HGOC. However, BRCAwt-unmethylated HGOC exhibited significantly lower HRD-, LOH- and ANTI-Scores when compared with BRCAmut (p &lt; 0.001) and BRCA1 meth -HGOC (p &lt; 0.005). All but one of the HGOC classified as platinum-refractory or -resistant at first relapse (92%) were BRCAwt-unmethylated. None of the BRCA1 meth cancers were rated platinum-refractory or -resistant at progression and only one of the BRCAmut cancers was associated with platinum-resistant first relapse. 99% of the recurrences from HGOC with genetically or epigenetically altered BRCA genes were platinum sensitive, from which 78% were classified as “high-sensitive”. In multivariate analysis, HRD-Score was found to be of independent prognostic significance regarding PFS (p = 0.022); this was mainly due to the prognostic power of ANTI-Score (multivariate: p = 0.014) but not to that of genome wide LOH (univariate: p = 0.771). Conclusions: HGOC without genetic or epigenetic BRCA alterations exhibit the most unfavorable PFS. This is related to impaired platinum sensitivity. From a clinical point of view BRCA1 promotor methylation seems to confer an equivalent detrimental effect on the homologous recombination DNA repair mechanism than do pathogenic mutations of the BRCA genes. This is corroborated by a nearly identical extent of genome-wide scaring in both cancer subgroups.